The roles of muscle contraction and insulin on restoring glucose uptake with novel pharmaceutical and engineering solutions

Immobilisation and inflammation are independently associated with significant muscle atrophy and when simultaneously present, result in catastrophic muscle mass loss that is associated with increased mortality. Muscle mass is maintained by the balance between muscle protein synthesis (MPS) and breakdown (MPB), with immobilisation rapidly supressing MPS resulting in muscle atrophy. Similarly, inflammation directly influences pathways modulating MPS, with ICU patients demonstrating reductions in MPS and muscle loss 100-fold increase in VL Il-6. Systemic inflammation is therefore likely to have significant damaging effects on whole body muscle, in addition to bed rest immobilisation post-surgery. Besides muscle, systemic inflammation often results in immune suppression. This immunoparesis is poorly understood, however there is an appearance of abnormal neutrophils with impaired function whose frequency is associated with increased susceptibility to infection and sepsis. As such there are no effective, feasible interventions to limit muscle atrophy after surgery or trauma, with the burden of systemic inflammation on muscle dysregulation and immunosuppression unknown.
This project will use novel stable isotope techniques developed to enable simultaneous measurement of MPS and neutrophil turnover during post-surgical recovery. Throughout the PhD the applicant will have access to world-class facilities and receive training from leading experts within the field of musculoskeletal research. Being based across two schools at the UoN the student will receive training on advanced metabolic and molecular biology techniques and learn cutting-edge mass-spectrometry techniques at the forefront of the field. Requiring blood and muscle biopsies to be collected the student will be familiarised with clinical skills and further spend valuable time at the Birmingham BRC developing skills and knowledge in inflammatory research and immunosuppression.